Sea cucumber (Holothuria nobilis) hydrolysates improve diabetic nephropathy via suppression of oxidative stress in high-fat diet/streptozotocin-induced diabetic rats

Abstract

Diabetic nephropathy (DN) is one of the most serious complications of diabetes. The purpose of the present study was to investigate the renoprotective effects of sea cucumber hydrolysates (SCH) produced using enzyme mixture of papain and protamex in diabetic rats and further to explore the underlying anti-oxidation mechanisms of peptides. Results showed that the activities of GSH-px and SOD were markedly increased by 16.97 % and 52.97 % respectively after SCH administration. Moreover, SCH increased the protein expression of NQO1, Akt, Nrf2 in kidney tissue of diabetic rats. Furthermore, 13 novel peptides were identified and further synthesized. Molecular docking analysis revealed that these peptides such as WWGP and APGY might directly bind to Keap1 through hydrogen bond, π-π bond or π-donor hydrogen bond, and thus modulate Akt/Nrf2 pathway. In summary, these findings suggested that SCH ameliorated oxidative stress by triggering Akt/Nrf2 signaling pathway, indicating that SCH may possess anti-diabetic nephropathy effects.

Keywords

• Peptide
• Diabetic nephropathy
• Oxidative stress
• Molecular docking
• Signaling pathway